Significant Improvements Also Observed in All Secondary and
Exploratory Measures

Conference Call and Webcast to Be Held Today, November 27, 2012, at
8:00 am Eastern Time

November 27, 2012 07:25 AM Eastern Standard Time

SAN DIEGO--(BUSINESS WIRE)--ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD) today announced successful
top-line results from its pivotal Phase III trial evaluating the
efficacy, tolerability and safety of pimavanserin in patients with
Parkinson’s disease psychosis (PDP). Pimavanserin is ACADIA’s
proprietary, non-dopaminergic product candidate that selectively blocks
serotonin 5-HT2A receptors. Pimavanserin met the primary
endpoint in the Phase III trial by demonstrating highly significant
antipsychotic efficacy as measured using the 9-item SAPS-PD scale
(p=0.001). Pimavanserin also met the key secondary endpoint for motoric
tolerability as measured using Parts II and III of the Unified
Parkinson’s Disease Rating Scale, or UPDRS. These results were further
supported by a highly significant improvement in the secondary efficacy
measure, the Clinical Global Impression Improvement, or CGI-I, scale
(p=0.001). In addition, clinical benefits were observed in all
exploratory efficacy measures with significant improvements in nighttime
sleep, daytime wakefulness and caregiver burden. Consistent with
previous studies, pimavanserin was safe and well tolerated in this Phase
III trial.

“These data represent an unprecedented advance for Parkinson’s patients
who suffer from the psychosis frequently associated with this disease,”
said Jeffrey Cummings, M.D., Sc.D., Director of the Cleveland Clinic Lou
Ruvo Center for Brain Health. “Among Parkinson’s patients, psychosis is
the leading cause of institutionalization and dramatically increases the
risk of mortality. Neurologists have limited options to treat this
serious disorder, and off-label use of current antipsychotics is linked
to increased risk of death and serious adverse events, as well as loss
of motor control. The results of this study suggest that a selective,
non-dopaminergic-based therapy has the potential to transform the
treatment landscape for patients with this debilitating disorder.”

Primary Endpoint

The primary endpoint of the trial was antipsychotic efficacy as measured
using the SAPS-PD, a 9-item scale adapted from the hallucinations and
delusions domains of the Scale for the Assessment of Positive Symptoms,
by comparing the mean change from baseline to day 43 for pimavanserin
versus placebo. SAPS-PD assessments were performed by blinded,
independent centralized raters. The pimavanserin arm demonstrated a
robust 5.79 point improvement in psychosis at day 43 compared to a 2.73
point improvement for placebo, representing a highly significant and
clinically meaningful treatment difference of 3.06 points on SAPS-PD
(p=0.001).

Baseline Mean

Mean Change at Day 43

PBO

PIM

PBO

PIM

P-value

(n=90)

(n=95)

SAPS-PD

14.73

15.88

-2.73

-5.79

0.001

Note: mixed model repeated measures (MMRM) method was applied in the
primary analysis of the intent-to-treat (ITT) population. The
significance test was based on least-square mean change from baseline
for each arm using a 2-sided beta = 0.05.

Key Secondary Endpoint

The key secondary endpoint of the trial evaluated motoric tolerability
and functional outcome using Parts II and III of the UPDRS. The
objective of this secondary endpoint was to demonstrate that
pimavanserin could achieve its antipsychotic effects without worsening
motor function as compared to placebo in PDP patients. A pre-specified,
non-inferiority analysis was used to compare the mean change from
baseline to day 43 for pimavanserin versus placebo using a two-sided 95
percent confidence interval (CI) for the treatment difference. Motoric
improvements were seen in both the pimavanserin and placebo arms and the
CI associated with the treatment difference did not exceed a
pre-specified margin of 5 points for clinically relevant change,
confirming that pimavanserin met this key secondary endpoint and did not
worsen motor function in PDP patients.

Secondary and Exploratory Efficacy Measures

The secondary efficacy measure in the trial was an assessment of
clinical global improvement by the investigator using the CGI-I scale.
Pimavanserin demonstrated a highly significant improvement on this
measure (p=0.001), further supporting its antipsychotic efficacy.

In addition, other clinical benefits of pimavanserin were observed in
exploratory efficacy measures of sleep and caregiver burden. Sleep was
assessed using the SCOPA-sleep scale, which was designed to enable the
investigator to evaluate nighttime sleep and daytime wakefulness in
Parkinson’s patients. Pimavanserin demonstrated significant improvements
on both nighttime sleep (p=0.045) and daytime wakefulness (p=0.012) on
SCOPA.

Caregiver burden was assessed using the Caregiver Burden Scale. This
scale was completed by the caregiver to provide a quantitative
assessment of burden associated with the patient’s functional/behavioral
impairments, the circumstances of at-home care, as well as the
caregiver’s health, social life and interpersonal relations.
Pimavanserin demonstrated a highly significant improvement on the
Caregiver Burden Scale (p=0.002).

Safety and Tolerability Profile

Consistent with previous studies, pimavanserin was safe and well
tolerated in this trial. Based on a preliminary analysis of safety data,
the most common adverse events were urinary tract infection (11.7% PBO
vs. 13.5% PIM) and falls (8.5% PBO vs. 10.6% PIM). Adverse events were
generally characterized as mild to moderate in nature. The only serious
adverse events that occurred in more than one patient were urinary tract
infection (1-PBO vs. 3-PIM) and psychotic disorder (0-PBO vs. 2-PIM).
Ninety percent of the patients who completed the clinical phase of this
trial elected to roll over into the ongoing open-label safety extension
study. Patients were only eligible to participate in the extension study
if the treating investigator also deemed them to be likely to benefit
from continued treatment with pimavanserin.

“We are excited with the results of this study which demonstrate that
pimavanserin has the potential to offer PDP patients a new treatment
option that, for the first time, can achieve the desired clinical
profile by providing an effective, safe and well tolerated antipsychotic
therapy,” said Uli Hacksell, Ph.D., Chief Executive Officer of ACADIA.
“We remain committed to advancing pimavanserin to registration as a
first-in-class treatment for this large unmet medical need. These
results also suggest that pimavanserin may have the ideal clinical
profile to address a broader range of neuropsychiatric disorders that
are underserved by currently marketed antipsychotics.”

“These significant and consistent top-line results are a strong
validation of the optimized study design used in this trial,” said Roger
G. Mills, M.D., ACADIA’s Executive Vice President of Development.
“Encouragingly, benefits of pimavanserin were seen by patients,
caregivers and investigators, as well as the independent raters.
Following the successful outcome of this pivotal Phase III trial, we
will continue our ongoing preparations for a confirmatory pivotal Phase
III trial, the -021 Study, using the same trial design.”

About the Trial Design

The pivotal Phase III trial, referred to as the -020 Study, was a
multi-center, double-blind, placebo-controlled study designed to
evaluate the efficacy, tolerability and safety of pimavanserin as a
treatment for patients with PDP. A total of 199 patients were enrolled
in the study and randomized on a one-to-one basis to receive either 40
mg of pimavanserin or placebo once-daily for six weeks, following a
two-week screening period including brief psycho-social therapy.
Patients also received stable doses of their existing anti-Parkinson’s
therapy throughout the study. The primary endpoint of the -020 Study was
antipsychotic efficacy as measured using the “SAPS–PD” scale, which
consists of nine items from the hallucinations and delusions domains of
the Scale for the Assessment of Positive Symptoms, or SAPS. These nine
items have been shown to be particularly relevant to the expression of
psychotic symptoms in patients with Parkinson’s disease and to have high
inter-rater reliability for assessment of severity. Motoric tolerability
was a key secondary endpoint in the study and was measured using Parts
II and III of the Unified Parkinson’s Disease Rating Scale, or UPDRS.

Conference Call and Webcast Information

ACADIA will host a conference call and webcast with slides today,
November 27, 2012 at 8:00 a.m. Eastern Time to present the top-line
results from its pivotal Phase III trial with pimavanserin in patients
with PDP. The conference call can be accessed by dialing 866-783-2140
for participants in the U.S. and Canada and 857-350-1599 for
international callers (reference passcode 26249437). The conference call
will be webcast live on ACADIA’s website, www.acadia-pharm.com,
under the investors section and will be archived there until December
11, 2012. A telephone replay also may be accessed through December 11,
2012 by dialing 888-286-8010 for participants in the U.S. and Canada and
617-801-6888 for international callers (reference passcode 47904115).

About Pimavanserin

Pimavanserin is ACADIA’s proprietary small molecule that acts
selectively as an antagonist/inverse agonist on serotonin 5-HT2A
receptors and is in Phase III development as a potential first-in-class
treatment for Parkinson’s disease psychosis. Pimavanserin can be taken
orally as a tablet once-a-day. ACADIA discovered pimavanserin and holds
worldwide rights to this new chemical entity.

About Parkinson’s Disease Psychosis

According to the National Parkinson’s Foundation, about one million
people in the United States and from four to six million people
worldwide suffer from Parkinson’s disease. Parkinson’s disease
psychosis, or PDP, is a debilitating disorder that develops in up to 60
percent of patients with Parkinson’s disease. Currently, there is no
FDA-approved therapy to treat PDP in the United States. PDP, commonly
consisting of visual hallucinations and delusions, substantially
contributes to the burden of Parkinson’s disease and deeply affects the
quality of life of patients. PDP is associated with increased caregiver
stress and burden, nursing home placement, and increased morbidity and
mortality. There is a large unmet medical need for new therapies that
will effectively treat PDP without compromising motor control in
patients with Parkinson’s disease.

About ACADIA Pharmaceuticals

ACADIA is a biopharmaceutical company focused on innovative treatments
that address unmet medical needs in neurological and related central
nervous system disorders. ACADIA has a pipeline of product candidates
led by pimavanserin, which is in Phase III development as a potential
first-in-class treatment for Parkinson's disease psychosis. ACADIA also
has clinical-stage programs for chronic pain and glaucoma in
collaboration with Allergan, Inc. and two advanced preclinical programs
directed at Parkinson’s disease and other neurological disorders. All
product candidates are small molecules that emanate from discoveries
made at ACADIA. ACADIA maintains a website at www.acadia-pharm.com
to which ACADIA regularly posts copies of its press releases as well as
additional information and through which interested parties can
subscribe to receive email alerts.

Forward-Looking Statements

Statements in this press release that are not strictly historical in
nature are forward-looking statements. These statements include but are
not limited to statements related to the progress and timing of ACADIA’s
drug discovery and development programs, either alone or with a partner,
including the commencement or progress of clinical trials and the
results of clinical trials, and the clinical benefits to be derived from
ACADIA’s product candidates, in each case including pimavanserin. In
particular, forward-looking statements include statements regarding the
potential implications of the results of the -020 study; the potential
for selective, non-dopaminergic-based therapy, such as pimavanserin, to
transform the treatment landscape for patients with PDP; the potential
of pimavanserin as a first-in-class, effective, safe and well tolerated
antipsychotic therapy and treatment for PDP; and the possibility that
pimavanserin may have a clinical profile suitable to address a broader
range of neuropsychiatric disorders that are underserved by currently
marketed antipsychotics. These statements are only predictions based on
current information and expectations and involve a number of risks and
uncertainties. Actual events or results may differ materially from those
projected in any of such statements due to various factors, including
the risks and uncertainties inherent in drug discovery, development,
regulatory review and commercialization, and in collaborations with
others, and the fact that past results of clinical trials may not be
indicative of future trial results. For a discussion of these and other
factors, please refer to ACADIA’s annual report on Form 10-K for the
year ended December 31, 2011 as well as ACADIA’s subsequent filings with
the Securities and Exchange Commission. You are cautioned not to place
undue reliance on these forward-looking statements, which speak only as
of the date hereof. This caution is made under the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995. All
forward-looking statements are qualified in their entirety by this
cautionary statement and ACADIA undertakes no obligation to revise or
update this press release to reflect events or circumstances after the
date hereof, except as required by law.